Interleukin-1beta and interleukin-6 increase levels of apolipoprotein B mRNA and decrease accumulation of its protein in culture medium of HepG2 cells.
The purpose of the present study was to examine the regulation of levels of apolipoprotein B (apoB) mRNA and its protein by cytokines in HepG2 cells. A dose-dependent increase in apoB mRNA levels was observed in the presence of either interleukin-1beta (IL-1beta) or IL-6 alone. This increase occurred as early as 1 h after IL-1beta or IL-6 stimulation. Exogenous addition of IL-1beta (5 ng/ml) and IL-6 (50 ng/ml) induced 2.8- and 2.1-fold increases as a result of 18 h of culture, respectively. Co-stimulation with IL-1beta and IL-6 significantly enhanced the increase in apoB mRNA levels stimulated with either cytokine alone. Treatment with cycloheximide prevented the induction of apoB mRNA by IL-1beta, but not by IL-6. These findings suggest that enhancement of apoB mRNA levels by these cytokines is mediated through different pathways. Conversely, IL-1beta and IL-6 lowered the accumulation of apoB protein levels in the culture medium. The pulse-chase study showed that addition of N-acetyl leucyl leucyl norleucinal to the medium induced a decrease in newly synthesized apoB in the cell lysate in response to IL-1beta (P < 0.05) or IL-6 (not to a significant extent) compared with control. These findings demonstrated that the lower level of apoB in the medium was caused by the enhanced intracellular degradation. In addition, IL-1beta increased LDL receptor mRNA levels as well as protein activity, although IL-6 did not, suggesting that the more marked decrease in apoB accumulation in the medium induced by IL-1beta compared with that induced by IL-6 may reflect an increased uptake of apoB from the medium by IL-1beta. The present study demonstrates that a cytokine network may be involved in the metabolism of apoB under certain conditions such as inflammation.
Yokoyama
K
K
First Department of Internal Medicine, Fukushima Medical College, Hikarigaoka, Japan.
Ishibashi
T
T
Yi-qiang
L
L
Nagayoshi
A
A
Teramoto
T
T
Maruyama
Y
Y
D001055:Apolipoproteins B / Q000235:genetics* / Q000378:metabolism; D017077:Culture Media, Conditioned; D003513:Cycloheximide / Q000494:pharmacology; D018197:Hepatoblastoma / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D011973:Receptors, LDL / Q000235:genetics; D014407:Tumor Cells, Cultured
D001055:Apolipoproteins B; D017077:Culture Media, Conditioned; D007375:Interleukin-1; D015850:Interleukin-6; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011973:Receptors, LDL; D003513:Cycloheximide